Mild-to-moderate chronic renal insufficiency (CRI) is reaching epidemic proportions in the US. Studies relating mild-to-moderate CRI and cardiovascular risk are limited and inconsistent. Although we have learned much about the natural history and adverse outcomes associated with end-stage renal disease (ESRD), we have little specific information regarding risk factors for the development or progression of renal disease. Using a population-based, ethnically diverse large cohort of male and female health plan enrollees with extended follow-up, we propose: Aim 1: To evaluate: a) whether baseline and decline in renal function overtime are independent predictors of coronary heart disease (CHID), stroke, heart failure and peripheral vascular disease; b) effect modifiers of these relationships, including baseline hypertension and diabetes status. Aim 2: To determine whether baseline and increase over time in blood pressure level (as well as prevalent and incident hypertension) are predictive of the subsequent risk of ESRD after adjusting for diabetes and for baseline serum creatinine, proteinuria and hematuria. Aim 3: To examine other potential predictors of ESRD including demographic factors (race/ethnicity, level of education) total cholesterol level, family history of renal disease, body mass index, sagittal abdominal diameter, cigarette (as well as cigar and pipe) smoking, coffee intake, alcohol consumption, family history of renal disease and self-reported occupational exposures. We will take advantage of existing longitudinal data resources at the Northern California Kaiser Permanente Division of Research and available patient-level cross-linkage with the US Renal Data System end-stage renal disease registry to obtain comprehensive renal and cardiovascular outcomes. A de novo prospective study of this magnitude and duration will be prohibitively expensive and time-consuming. This proposal will leverage unique resources and methodological expertise to provide novel insights into the epidemiology of renal disease and its association with cardiovascular events.